Mitochondria provide the majority of the body’s energy supply and are considered the power plants of the cells. The energy comes from cellular respiration, in which metabolic products are burned in the inner mitochondrial membrane. Mitochondria also play an important role in the metabolism of cells, both in the breakdown and synthesis of numerous cell building blocks. Many of these processes depend on proteins in the inner membrane, which has an extraordinarily high protein density. Defects in these proteins lead to serious diseases in humans. A team led by Dr. Heike Rampelt and Nikolaus Pfanner from the Institute of Biochemistry and Molecular Biology at the University of Freiburg has now discovered a new mega-protein complex with surprising properties in the inner mitochondrial membrane. Their findings have been published in the journal Cell Reports.
Like specialized assembly line workers
The new complex is called MIMAS(mitochondrial multifunctional assembly); it is named after a giant in Greek mythology because of its unusual size. It integrates numerous different processes into a common platform - thus deviating from the previous paradigm that the components of a protein complex typically perform a common function.As the research team was able to show, MIMAS combines very different functions in contrast to the established mitochondrial protein complexes: it comprises numerous factors that assemble the respiratory chain complexes like specialized assembly line workers. In addition, there are diverse transport proteins that transport ions or metabolic products between mitochondria and the rest of the cell, as well as enzymes involved in energy metabolism and membrane lipid synthesis.
Astonishing functional diversity
This astonishing functional diversity in MIMAS is not the only special feature of the complex: its stability also depends on a specific membrane lipid whose synthesis enzyme is itself a MIMAS component. These observations suggest that MIMAS is the founder of a novel organizing principle in the inner mitochondrial membrane: proteins of different functions are organized in a megacomplex, which could be an important target for regulation, for example in metabolic changes or diseases.- Original publication: Horten, P., Song, K., Garlich, J., Hardt, R., Colina-Tenorio, L., Horvath, S.E., Schulte, U., Fakler, B., van der Laan, M., Becker, T., Stuart, R.A., Pfanner, N., Rampelt, H.: Identification of MIMAS, a multifunctional mega-assembly integrating metabolic and respiratory biogenesis factors of mitochondria. In: Cell Reports 43, 113772.
DOI: 10.1016/j.celrep.2024.113772.
Preview article about the study: Tokatlidis, K.: MIMAS is a new giant multifunctional player in the mitochondrial megacomplex playground. In: Cell Reports 43, 113874.
DOI: 10.1016/j.celrep.2024.113874 - The study was carried out in collaboration with the working groups of Dr. Uwe Schulte and Dr. Bernd Fakler from the University of Freiburg, Rosemary A. Stuart from Marquette University in Milwaukee/USA, Thomas Becker from the University of Bonn and Martin van der Laan from Saarland University in Homburg. The research work involved numerous biochemical methods and mass spectrometric analyses.
- Dr. Heike Rampelt and Nikolaus Pfanner lead working groups at the Institute of Biochemistry and Molecular Biology at the Faculty of Medicine, Dr. Uwe Schulte and Bernd Fakler at the Institute of Physiology at the University of Freiburg. They all conduct research at the Freiburg Cluster of Excellence CIBSS in the field of biological signaling research.
- The study was funded by the German Research Foundation (DFG) and the Cluster of Excellence CIBSS at the University of Freiburg.
